Chemical analysis of Plakortis simplex sponge extract provided a number of structurally unique secondary metabolites, including the antimalarial polyketide plakortin, the IL-10 inducing simplexide and other unusual glycolipids, and hopanoids. The hypothesis that they could be products of symbionts was explored by a multi-step strategy: i) cell separation of the fresh sponge tissue in combination with chromatographic and spectroscopic analysis; ii) PCR experiments to prove the presence of key enzymes of the biosynthesis of glycolipids and polyketides; iii) cultivation and screening of GSL-producing bacteria; iv) screening of metagenomic DNA of P. simplex in search of a PKS compatible with the structure of plakortin
